A productive infection by vaccinia virus involves entry into the cell; expression and replication of the genome; defense against specific and non-specific host immune mechanisms; and assembly and release of infectious, enveloped, virus particles. Many of these steps involve interactions of viral proteins with cellular proteins or membranes. Combined genetic, biochemical, and electron microscopic approaches are being used to investigate these complex processes. During the past year, emphasis has been on understanding the steps in the formation and transmission of intracellular and extracellular virions, the host range restriction of poxviruses, and viral immune defense proteins.